Over 1.3 million age-related fractures occur annually in the U.S. including approximately 250,000 fractures of the hip, 550,000 of the spine and 250,000 of the wrist. Annual costs for treatment are thought to exceed $10 billion are expected to grow to more than $30 billion in the next 30 years. As measured by their frequency, influence on quality of life and economic cost, age-related fractures among the elderly are a public health problem of crisis proportions. Within successful initiatives aimed at reducing their incidence, the implications for the allocation of health resources in this and the next century are staggering. Interventions to reduce the prevalence of age-related fractures must be based on a sound understanding of fracture etiology, on agents and approaches of demonstrated efficacy and cost effectiveness, and on diagnostic, screening and therapeutic monitoring procedures. of appropriate accuracy, precision and sensitivity. In this research program, we continue to address the development of new densitometric tools of increased diagnostic sensitivity and predictive accuracy. Our objectives in the first three years were to characterize the relationships between bone geometric and densitometric properties determined by a new multiscan Dual Energy X-Ray Absorptiometry (DXA) technique and bone fracture loads at the distal radius and proximal femur. We showed: 1) multiscan DXA parameters are highly predictive of distal radius fracture loads (r2=0.67,p,0.0001) whereas conventional measures of BMD at the distal radius are not (r2= 0.07, p .0.1);2) multiscan DXA parameters and BMD at the femoral neck are good predictors of fracture load in the proximal femur (r2=0.740 but conventional BMD measures at intertrochanteric sites are not (r2=0.12, p=0.10); and 3)fracture loads at the distal radius are poor predictors of fracture load at the hip. These findings have important implications for the use and interpretation of conventional densitometry an suggest athe further development of DXA techniques are warmed. In this competitive renewal we propose to extend our findings in two significant ways. First, in Specific Aims 1 and 2, we plan to test the discriminatory power of DXA geometric variables in two case-control clinical studies (a retrospective review of available DXA scans from a separately funded falls surveillance study and a new observational study of spontaneous hip fracture patients and their age- and gender-matched controls). Second, in Specific Aims 3 and 4, we will extend our DXA methodology to the spine and thereby allow conventional and geometric DXA and fracture load comparisons to be made for the first time between all three high fracture risk regions within the same cadaveric specimen. We expect the study of spontaneous fracture to yield a much stronger densitometric separation between hip fracture patients and controls since the data will not be confounded by issues related to fall severity and traumatic loading. We hope to provide (even for conventional densitometry) more realistic estimates of the fracture risk threshold associated with activities of daily living and thus better targeting of candidates at risk for true fragility fractures of the hip.